IgG antibody and TH1 immune responses to influenza vaccination negatively correlate with M-protein burden in monoclonal gammopathy of undetermined significance

Background: The emergence of non-malignant conditions such as monoclonal gammopathy of undetermined significance (MGUS) in the elderly may further alter their increased susceptibility to infections, however this remains poorly defined. The immune response to influenza vaccination has not been examined in MGUS, a benign plasma cell monoclonal expansion in the bone marrow that secretes elevated levels of monoclonal immunoglobulin (M-protein). Pre-existing antibody titers to infectious agents can be depressed, but the degree of immunosuppression in response to active vaccination remains unclear. Furthermore, the association of M-protein levels with impaired antigen specific response has not been examined to date in MGUS. Methods: We investigated antibody as well as T cell responses in 19 MGUS patients and age-matched healthy controls following influenza vaccination. H1N1 and H3N2 influenza-specific IgG antibodies were measured by ELISA. The frequencies of H1N1 and H3N2 specific IFN-γ secreting cells were measured by ELISpot. Results: Polyclonal isotype-switched immunoglobulin levels were significantly reduced in the MGUS cohort (p<0.05). At the cohort level, HIN1 and H3N2 influenza-specific IgG titers were comparable in MGUS and HCs. However, a key distinction emerged in relation to M-protein levels. MGUS patients with high M-protein had decreased influenza specific IgG titers which they failed to expand post-vaccination. Low M-protein MGUS H1N1-specific IFN-γ responses were high and comparable with HCs but showed no discernible increase post-vaccination, while cellular responses to H1N1 in high M-protein MGUS were markedly reduced. Conclusions: Overall, MGUS showed depressed immune responses to influenza vaccination that varied strikingly with M-protein levels.